Nucleophilic Substitution at a Carbonyl Carbon Atom (V). Kinetic Studies on Halogen Exchange Reactions of N,N-Dialkylcarbamoyl Chlorides in Dry Acetone

DAEHAN HWAHAK HV/OEJEE

(Journal of the Korean Chemical Society) Vol. 19, No. 1, 1975

Printed in Republic of Korea

카르보닐 탄소원자의 친핵치환 반응제

보). 아세톤 용매속에서의

^{의 할로겐}

교환반응에 관한 속도론적 연구 金 時 俊•李 益 春*

한양대학교 교양학부 화학과

*인하대학교 이과대학 화학과

(1974. 11. 27 접 수)

Nucleophilic Substitution at a Carbonyl Carbon Atom(V).

Kinetic Studies on Halogen Exchange Reactions of N, A^-Dialkylcarbamoyl Chlorides in Dry Acetone

Shi Choon Kim and Ik Choon Lee우

Department of Chemistry, College of General Studies, Hanyang Universityt Seoul, Korea.

^Department of Chemistry, Inha University, Inchon, Korea

(Received Nov. 27, 1974)

유 약 Carbonyl 탄소원자의 반응성 에 대 한 연구의 일환으로 N, N-dimethylcarbamoyl chloride 와 N, N-diethylcarbamoyl chloride 의 할로겐 교환반응을 아세 튼 용매 속에 서 방사성 할 라이 드 이 온을 사 용하여 두 온도에서 속도론적으로 연구하였다.

그 결과를 alkylchloroformate 의 경 우와 비 교하면, 친핵성 의 순서는 비 슷한 경 향을 나타내나, 반응 속도는 가용매 분해 나 alkyl사iloroformate의 경 우보다 느리 다, 활성 화 피 라미 터 나 0S*는 C「〉

의 순서로 감소한다. 이 결과를 용매화 효과, bond-breaking, bond-formation 및 electronic requirment로 설명하였다.

Abstract Kinetic study of halogen exchange for N, N—dimethylcarbamoyl chloride and N, N—diethyl- carbamoyl chloride in acetone by using radioisotopic halide ions has been carried out at two tempera­

tures as a part of studying the reactivity of carbonyl carbon atom.

The order of nucleophilicity showed a similar tendency as that for alkyl chloroformate, but reaction rate is much slower than that for solvolysis and alkyl 사iloroformate.

The activation parameters, /H* and 4S* were found to decrease in sequence Cr>Br">I~ for N, AMialkylcarbamoyl chlorides.

The results are interpreted in terms of solvation e仟ect, degree of bond-breaking and bond-formation and electronic requirments.

— 11 —

12

Introduction

Carbonic acid chlorides show interesting features in nucleophilic substitution mechanisms; all three types of substitution at a carbonyl carbon atom, S^l1, S必 and SAN3 (addition-elimination), have been demonstrated depending on nucleophiles and solvents. Alkyl chloroformates4 and benzoyl halides5 are reported to react with amines by SaN mechanism, which involves an addition intermediate (I).

0 0~

II I

R —C—X + N= R —C—N froduct .I

X (I)

Structurally dialkylcarbamoyl chlorides form a special class of carbonic acid chlorides in. that these have strong electron donating group.

Ostrogovich, et al. 6 has shown that in all hy­

drolysis of carbamoyl chlorides the powerful meso­

meric electron donation of the dialkylamino-group strongly stabilizes the acylium ion and favors the SnI mechanism.

R2NCOCI 二=r2nc+-o + Cl-

R?NC+=0 4- HOR ―> R2NCO2R + H+

However in the reaction with amines7, carba' moyl chlorides exhibited relatively large S values (5—2.0) of the Swain-Scott equation and there­

fore the reaction seemed to proceed via an S%2 process.

In this work, we have used dimethyl- and di- ethylcarbamoyl chloride in order to see how much of the Sn\ character is retained in halogen ex­

change reactions of these compounds in view of the fact that the halide nucleophiles are generally less reactive as compared to amines.

Experimental

1. Materials N, JV-Dimethylcarbamoyl chlo­

ride and N, N-diethylcarbamoyl chloride (Merk Germany) were purified by distillation under reduced pressure.

LiCl, (C2H5)4NBr and KI were Merk G.R.

reagents, which were used without further puri­

fication.

Acetone was purified by drying over calcium chloride before fractional distillation usin응 a Todd Colume(reflux ratio 10-1) and was dehydrated by flowing through the alumina colume. This treatment reduces the water content to 0.08% or less8.

Radioactive Cl36 (HC1 form) and I125(NaI form) purchased from the Radiochemical Center, Amersham, Bik시:inghamshire, England, and Br82((C2H5)4NBr form) was supplied by the Radioisotope Production Group of Atomic Energy Research Institute, Korea.

2. Kinetic Runs were Conducted as De­

scribed before9 Cl36 activity was counted by using Aloka-1600 Liquid Scintillation (Counter, and Br82 and I125 activities were measured by using Well-type Scintillation Counter.

Exchange rates were calculated by the equation

for chloride exchange, and

for bromide and iodide exchange reaction where a and b are initial concentration of substrate and salt, respectively, and

g=¥)+K+物 D=(K'2 + 4K"/2

where K is the ion pair dissociation constants in acetone, F is the fraction reacted at time a is the degree of dissociation of salt.

Activation parameters were calculated by ge­

neral method based on absolute rate theory10.

Journal of the Korean Chemical Society

카르보닐 탄소원자의 친핵치 환 반응（제 5보） ₁₃

The plot of —log(l—F) versus t was linear. A typical plot is given in Fig. 1.

The rate constant determined in this way pro­

ved to be reproducible to ±5%. Thus the accu­

racy of 4H* andwas estimated dzl. Okcal/

mole and zh2e. u, respectively. The accuracy of andwill not improve greatly even though they were calculated with rate constant at more than two temperatures. Therefore we have determined the activation parameters from rate constants, k, at two temperatures since we are only concerned with general trends of the activation parameters in this work.

&

i x£ i i) m-

—

a—

--- * time t(min)

Fig. 1. A typical plot of 一log(l—F) vs. t of chloride-chloride exchange at 65°C and 70°C for the reaction

(CH3)2NCOC1 + cf- t (CH3)2NCOC1* 4- ci-

Result and Discussion

The rate constants measured are given in Table 1.

Rate constants in Table 1 show that the order of reaction rate coincides with the order of nu­

cleophilicity of halides in dipolar aprotic solvent11 such as acetone, i, e, as was expected.

The rate of halogen exchange of N, N-diaL kylcarbamojd chlorides is much slower than that of solvolysis shown in Table 2 considering the difference in reaction temperatures of the two reactions.

The rate constant for chlorine exchange in N, A-dimethylcarbamoyl chloride is smaller than that of N9 IV-diethylcarbamoyl chloride. This is the same trend as that obtained in the sol­

volysis where the successive substitution of methyl groups at a-carbon increased the rate from (CH3) 2N- to (iso-CsH?) 2N- compounds. This was interpreted as the result of increasing acylium ion stabilization.6 Thus the rate sequence implies that chlorine exchange of dialkylcarbamoyl chlorides in acetone also involves considerable

degree of SnI character if not a limiting

Table 1. Summary of rate constants k(M~-sec~') for halide exchange of N, N-dialkyL- carbamoyl chloride in aceton.

R2NCOCI 十y-->r2ncoy + Cl-

r2 _(°C)

CI' Bf I"

(CH3)2-

60 7- 72X10-4 1

65 2. 80X10-3 3. 30X10'5 1.55X10-5

70 4. 49X10-3 4. 92X10-5 2. 02X10-5

(C2H5)2-

50 1. 61X10"3

60 2.60X10-3

65 5. 54X10-3 2.18X10-5 1.31X10-5

70 3. 04X10녀 ^1.78X10-5

We therefore suggest that halogen exchanges in dialkylcarbamoyl chloride proceed via the transition state where bond-breaking progressed more than bond-forming. On the other hand the order of reactivity of nucleophiles, i. e, Cl~〉 B广〉I、shows that the exchange of halogen is a typical S^2 process. Consequently the reaction may be characterized by an S^2 direct displace­

ment with the greater importance of bond-break­

ing than bond-forming in the transition state.

Additional information can be obtained from the activation parameters shown in Table 3.

Comparison of activation parameters in Table 3 with those for the hydrolysis reaction in Table 2 shows that while the values are much the same, thevalues differ considerably. This may be interpreted as there is little difference in bond-breaking energy while marked difference exists in entropy changes in the activation proc­

ess. Large difference in values car be ex­

plained if we assume that the bond-breaking 益春

has progressed further than the bond-forming at the transition state as we have already suggested in the above discussion. If this is the case, developing charges on the carbonyl ca호bon and halogen atom will require some additional elec- tro다riction at the transition state and this effect will be greater in acetone than in water since in the latter there is some structure originally present at the initial state12. Thus the negative entropy change in forming two partial charges at the transition state from the initial state is smaller in water since the breaking of pre-exis­

ting water structure will give positive contribu­

tion to 4S* value.

The magnitude of activation parameters follow the order of nucleophilicity i.e, Cl_^>Br->I- for halogen exchanges in dialkylcarbamoyl chlorides.

If we assume the same extent of bond-breaking for all the exchanges of halides, this will mean that the extent of bond-forming has progressed in the same order,

Table 2. Rate constants and activation parameters for the hydrolysis in water-acetone (1: 1V/V) of M Ar-dialkylcarbamoyl chlorides (at 30cC)*

10,。士 力)/seL /H 노 (kcaLmolL) u)

(CH3)2NCOC1 3.27±0.01 : 20.4 —2. 6

(C2H5)2NCOC1 丨 25.4 士 0.4 18-3 -5.8

(z-C3H7)2NCOC1 i 159—0.7 7.35 -37.8

*from R. Bacalo음lu, el al. , J. C. S. Perkin II, 1011, 1972.

(R)2NCOC1 + y- —> (R)2NCOY + ci-

Table 3. Activation parameters for halogen exchange of N, N-dialkylcarcarbamoyl chloride in acetone.

g 1I

Y~

ci- Br- r

(CH3)2

-(kcal/mole) 21.2 17.8 11.5

(e. u) — -26.5 -46.8

(C2H5)2

4H干(kcal/mole) 17.2 14-7 13.6

(e. u) -18.3 -33.6 —40.9

Journal of the Korean Chemical Society

카르보닐 탄소원자의 친핵치환 반응제 5보） 15

1'•

部

c - -

m

on e——

R on e——

R ohc i. R

since the bond-formation requires overcoming of repulsive energy13 and dispersion of charge re­

sulting entropy increase.

Table 4 shows the rate constants for halogen exchanges in alkylchioroformates ROCOCI in acetone14. It is seen readily from this Table that k value for this reaction is much larger than that for carbamoyl chlorides. The halogen exchange of alkylchioroformates is reported to involve an addition-elimination, S&N, mechanism14. This is, therefore, different basically from the reaction studied in this work. It has been shown that in the case of chloroformate14 the bond-formation is almost complete at the transition state while for Table 4. Summary of rate constants 为(molesec"1)

for halide exchange of alkylchloroformate in acetone*

r一 o — COCI + Y" t R — 0 —COY + Cl-

R

Y'

ci- Br~ r

CH3- 1.98X10"1 (20°C)

8. 75X10-3 (20°C)

6. 51X10-3 (25. 3°C)

C2H5— 5- 14X10'2 (20。。)

7. 56X10-4 (20°C)

4. 03X10-4 (30°C) from Ref (3)

carbamoyl chloride bond-breaking has much more progressed than bond-forming.

Thus the basic difference in mechanism can be understood from the transition state structure.

References

1. A. Queen, T. A. Nour, M.N. Paddon-Row and K. Preston, Can. J. Chem, 48, 522(1970).

2. H.K. Hall, Jr, J. Amer. Chem. Soc., 77, 5993 (1955).

3. M.L. Bender, Chem. Revs,, 60, 53(1960).

4. G. Ostrogovich, C. Csunderlik and R. Bacaloglu, J. Chem. Soc. (B), 18(1971).

5. L. M. Litvinenko and G. V. Semenyuk, Organic Reactivity, U. S. S. R., 7, 1083(1970)； V. A. Sa- velova and L. M. Litvinenko, ibid., 5, 838 (1968).

6. R. Bacaloglu, C. Daescu and G. Ostro응ovich, J. C. S. Perkin II, 1011(1972).

7. H.K. Hall, Jr., J. Org. Chem., 29, 3539(1964).

8. E. Mueller, "Methoden der Organische Chemie"

4th Ed., P. 163, Georg Thieme Verlag, Stutt­

gart, 1958.

9. I. Lee and J. E. Yie, J. Korean Chem. Soc., 17, 154(1973).

10. S. Glasstone, K. J. Laidler and H. Eyring, “The Theory of Rate Processes” Chapt. IV, McGraw- Hill Book Co., New York, 1941.

11. S. Winstein, L. G. Savedoff, S. Smith, I. D. R.

Stevens and J. S. Gall, Tetrahedron Lett., 9, 24 (I960).

12. L. L. Schaleger and F. A. Long, uAdvances in Phys. Org. Chem”，Vol. 1, P. 1, Ed. by V.

G사d, Academic Press, London, 1963.

13. R. F. Hudson and G. Klopman, J. Chem. Soc.t 1062(1962).

14. B. S. Lee and I. Lee, J. Korean Chem. Soc., 18, 223(1974).